In a study published in February, a team of U.S. and Swiss researchers shed light on how interferon prevents the human immunodeficiency virus (HIV) from replicating. The lead investigator of the study was Satish K. Pillai, PhD, assistant professor of medicine at the University of California, San Francisco, and the San Francisco VA Medical Center.
Interferons, naturally occurring proteins manufactured by immune system cells, are also developed commercially using recombinant DNA technology. Once commonly prescribed for patients early in the HIV epidemic, interferon is now rarely used by itself. However, it is still used in combination with other drugs, such ribavirin, to treat patients with the hepatitis C virus (HCV). How interferon works to prevent viral replication was not previously known.
For the study, Pillai and his colleagues identified 20 patients infected with both HIV and HCV who were enrolled in the Swiss HIV Cohort Study, which began in 1988. All of the subjects were taking interferon to treat their HCV, though none were receiving HIV antiretroviral drugs. This allowed investigators to examine how interferon suppresses HIV using restriction factors (RF), chemicals produced by the immune system.
While other components of the immune system send whole cells to destroy pathogens, RFs use a more targeted, clandestine approach. One RF, called APOBEC3, combats viruses by attaching itself to viral particles while they are still forming. It then sabotages HIV’s genetic makeup, blocking its ability to replicate. Another RF, aptly named tetherin, holds virus particles in place as they emerge from infected cells. Unable to move, the HIV particles cannot infect other cells. Undaunted, HIV then launches a counter attack, producing proteins that combat the RFs.
Pillai and his team discovered that interferon fights HIV by “mediating” the action of both of these restriction factors. They collected blood samples from the 20 patients and measured the levels of APOBEC3 and tetherin before, during and after the subjects took interferon. The levels increased in response to interferon when the drug was in the bloodstream. Patients with the highest RF levels showed the most precipitous drop in HIV viral load during interferon treatment.
This new understanding of interferon may help scientists boost the RF defense system by enhancing the expression of APOBEC3 and tetherin in people with HIV.
The study, “Role of retroviral restriction factors in the interferon-α–mediated suppression of HIV-1 in vivo,” was published online February 6, 2012, in the Proceedings of the National Academy of Sciences.